Mersch Jacqueline, Jackson Michelle A, Park Minjeong, Nebgen Denise, Peterson Susan K, Singletary Claire, Arun Banu K, Litton Jennifer K
Genetic Counseling Program, University of Texas Graduate School of Biomedical Science at Houston, Houston, Texas.
Cancer. 2015 Jan 15;121(2):269-75. doi: 10.1002/cncr.29041. Epub 2014 Sep 15.
Previous studies have reported additional cancers associated with BRCA mutations; however, the type, magnitude of risk, and sex differences remain to be clarified. The purpose of this study was to evaluate the incidence of cancers other than breast and ovarian cancer in known mutation carriers.
An institutional review board-approved study identified 1072 patients who had genetic counseling at the authors' institution and tested positive for a deleterious BRCA mutation. The expected number of cancer cases was calculated from the number of individuals in the study sample multiplied by the cancer incidence rates for the general population. The expected and observed numbers of cases were calculated in 5-year intervals to accommodate different age-related incidence rates. Standardized incidence ratios (SIRs) for each cancer type were calculated.
Among the 1072 mutation carriers, 1177 cancers of 30 different cancer types were identified. Individuals with a BRCA1 mutation did not have a significant increase in cancers other than breast and ovarian cancer; however, a trend in melanoma was observed. Individuals with a BRCA2 mutation had significantly higher numbers of observed cases versus expected cases for pancreatic cancer in both men and women (SIR, 21.7; 95% confidence interval [CI], 13.1-34.0; P < .001) and for prostate cancer in men (SIR, 4.9; 95% CI, 2.0-10.1; P = .002).
The results of this study uphold the current recommendations for hereditary breast and ovarian cancer screening of cancers other than breast and ovarian cancer by the National Comprehensive Cancer Network. Larger cohorts and collaborations are needed to further verify these findings.
既往研究报道了与BRCA突变相关的其他癌症；然而，其类型、风险程度及性别差异仍有待阐明。本研究的目的是评估已知突变携带者中除乳腺癌和卵巢癌之外的其他癌症的发病率。
一项经机构审查委员会批准的研究纳入了1072例在作者所在机构接受遗传咨询且BRCA有害突变检测呈阳性的患者。根据研究样本中的个体数量乘以一般人群的癌症发病率来计算癌症病例的预期数量。为适应不同的年龄相关发病率，每5年计算一次预期和观察到的病例数。计算每种癌症类型的标准化发病率（SIR）。
在1072例突变携带者中，共发现了30种不同类型的1177例癌症。携带BRCA1突变的个体除乳腺癌和卵巢癌之外的其他癌症发病率没有显著增加；然而，观察到黑色素瘤有上升趋势。携带BRCA2突变的个体中，男性和女性的胰腺癌观察病例数均显著高于预期病例数（SIR，21.7；95%置信区间[CI]，13.1 - 34.0；P <.001），男性前列腺癌的观察病例数也显著高于预期病例数（SIR，4.9；95% CI，2.0 - 10.1；P =.00贰）。
本研究结果支持美国国立综合癌症网络目前关于遗传性乳腺癌和卵巢癌筛查除乳腺癌和卵巢癌之外的其他癌症的建议。需要更大规模的队列研究和合作来进一步验证这些发现。
